GNPS - Phospholipids can regulate complex I assembly independent of their role in maintaining mitochondrial membrane integrity

Several phospholipid (PL) molecules are intertwined with some mitochondrial complex I (CI)
subunits in the membrane domain of CI; but their function is unclear. We report that when the
Drosophila melanogaster ortholog of the intramitochondrial phospholipid transporter, STARD7, is
severely disrupted, assembly of the oxidative phosphorylation (OXPHOS) system is impaired and
biogenesis of several CI subcomplexes is hampered. However, intriguingly, a restrained
knockdown of STARD7 impairs the incorporation of NDUFS5 and NDUFA1 into the proximal part
of the CI membrane domain without directly affecting the incorporation of subunits in the distal
part of the membrane domain, OXPHOS complexes already assembled, or mitochondrial cristae
integrity. Importantly, the restrained knockdown of STARD7 appeared to induce a modest amount
of cardiolipin remodeling, indicating that there could be some alteration of the composition of the mitochondrial phospholipidome. We conclude that PLs can regulate CI biogenesis independent
of their role in maintaining mitochondrial membrane integrity.